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Influenza

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INFLUENZA. The term influenza will be used to imply "a pandemic outburst of disease characterized, clinically, by a rapid course, catarrh of the respiratory tract, pyrexia and some degree of prostration; and epidemiologically, by a tendency to occur in several successive waves at short intervals of time." This pro visional definition is applicable to the visitation of 1918-19, and to other outbreaks of febrile respiratory catarrh more remote in time and about the distribution of which less is known, but is not applicable to the sporadic cases or even the localized epi demics of respiratory catarrh to which the name influenza has been so often applied, especially in the years following fairly closely upon pandemic outbursts.

The Influenza Pandemic of 1918-19.

This pandemic swept over the world in three successive waves, the first appearing quite suddenly in May and June 1918, the second starting at the end of September or early in October and waning in December, and the third wave, less uniform in character, appeared early in March 1919. This outbreak, attributed by France to Spain, by Spain to France and by America to eastern Europe, seems to have appeared almost simultaneously amongst the nations on the West ern front, and showed the explosive character that is possible only for a highly invasive infection assisted by conditions of swift communication such as obtain in modern war.

This first wave made its appearance a little later amongst the Central Powers and their neighbours. Early in July it attained its full proportions in Germany, Austria, Norway, Sweden and Denmark, Holland and Switzerland. In several large areas of the world's surface, in the South American republics, in Bermuda, the British West Indies, the Azores and in the islands of the Pacific and Australia, the summer of 1918 passed without an influenzal outbreak. In New Zealand, cases are said to have appeared in August, the harbingers, perhaps, of the autumn, rather than the first manifestations of the summer, wave.

This first wave passed rapidly, so that a "frequency curve" by weeks, in which the incidence in the worst week is taken as T00%, shows a steep ascent to a maximum, followed by an equally steep and almost symmetrical fall, the whole episode passing within a few weeks. The death-rate was inconsiderable, but there was an ominous tendency to a higher mortality amongst the later cases, just before the wave came to an end, seeming to suggest an increase in virulence. The first batch of cases looked "like a mild attack of measles without a rash." Respiratory catarrh, congested conjunctivae, headache, lassitude, pyrexia of short duration, a feeling of prostration with the return of temper ature to normal, and then a rapid recovery of health; such was the course in the vast majority of the cases during the first wave. Complications were almost unknown. A few cases which de veloped broncho-pneumonia or haemorrhagic oedema of the lungs towards the end of the wave sent up the case mortality. In all these characters, the first wave closely resembled the outbreak of 189o, except that in 1890 the death-rate was greatest amongst the middle-aged and elderly, while in 1918 the chief sufferers were amongst the "young adult" groups.

The Second Wave.

Towards the end of September or early in October, the second wave suddenly gathered force and swept over the world. St. Helena is said to have escaped. Mauritius, too, had a reprieve ; and the quarantine measures applied by Australia were successful for the moment but this fatal pandemic spread throughout Europe, America, Asia and Africa.

The upward curve of morbidity was almost precisely similar to that of the summer and the maximum was reached as quickly as in the previous wave, but the fall was much slower and less regular. The outstanding difference between the two waves was the marked tendency to pulmonary complications and the high death-rate of the second. The singularly uniform syndrome of the summer epidemic gave place, in the autumn, to several vari eties of clinical picture depending on varying combinations of several factors, amongst which might be reckoned the virulence of the microbic invader, the resistance of the patient, the nature of the bacterial flora of his respiratory tract, and environmental conditions such as occupation, wages and housing. As a rule, the attack was ushered in by the catarrhal and pyrexial symp toms noted in May and June. In many cases, especially where circumstances permitted of immediate rest and treatment, the disease took a favourable course towards recovery, although prostration was clearly always a more marked feature than in the summer. In others, the early pyrexial catarrh was sometimes followed by intense toxaemia leading so rapidly to a fatal issue that there was no time for pulmonary complications to develop. But frequently the lungs became severely affected and the pa tient passed into a state of anoxaemia recalling that due to exposure to the "pulmonary irritants" of gas warfare.

But there was a formidable difference between the two condi tions. While the "phosgene" patient had to deal with a sterile exudate, evoked by a chemical irritant and capable of rapid ab sorption if vitality was maintained, the lungs of the influenza patient were charged with an exudate evoked by a living virus which had already overcome tissue resistance and could offer to "secondary invaders" conditions of symbiosis favourable to their growth. Here lay the danger. The virus of influenza could open, as it were, the door to the streptococci, pneumococci, staphy lococci and other organisms normally held within safe numerical limits upon the respiratory mucous membrane. The post-mortem appearances, while tending to have certain basal characters in common, varied considerably with the nature of the "secondary invaders" and other factors. In nearly all cases, there was a haemorrhagic tendency not often seen in other acute lung affec tions; and this sometimes amounted to a haemorrhagic oedema involving the greater part of both lungs. "Wet lungs," "drip ping lungs," were expressions frequently heard in the post-mortem room. Areas suggesting haemorrhagic infarcts with their bases extending under the pleura were often noticed. The cut surface of the lungs showed, as a rule, peribronchiolitis and patches of broncho-pneumonia with a general state of oedema throughout the parenchyma of the lung; or a whole lobe might give the ap pearance of red, or in older cases, grey hepatization (see Major Tytler, R.A.M.C., Special Report Series No. 36, Med. Res. Coun., 1919). The third wave had no distinctive characters. It resem bled the first wave rather than the second, though pulmonary complications and fatal cases were fairly numerous.

Etiology.

As to the causative organism of influenza we re main, even now, still in doubt. The view that the Bacillus influ enzae (Pfeiffer) was the cause of the disease, received little sup port from investigations carried out since 1918. This work was directed, for the most part, to the search for a "filter-passing virus." During the second wave of 1918, the researches of C. Nicolle and Lebailly in the French war zone, of H. G. Gibson, F. B. Bowman and J. I. Connor at Abbeville, and of J. A. Wilson at Staples, in the zone of the British armies in France, afforded highly significant evidence in favour of a filterable virus, although the restrictions imposed upon bacteriological work by war con ditions and the transitory nature of the epidemic rendered conclu sive findings impossible.

In 1919, an investigation was undertaken by Zamanouchi, Sakakami and Iwashrima, in which the filtered and unfiltered emulsions of sputum from 43 cases of influenza were injected into the throats and noses of 24 healthy volunteers, six of whom had recently suffered from influenza. Of the 18 previously un infected persons, all developed influenza of ter an interval of two or three days, but the six who had had the disease remained in good health. Similar results were obtained with the filtered blood of patients. At the same time, the spraying of cultures of Pfeif fer's bacillus, sometimes "pure," sometimes mixed with other respiratory bacteria, into the throats of 14 healthy persons failed to lead to illness of any kind.

P. K. Olitsky and F. L. Gates in the laboratories of the Rocke feller Institute for Medical Research were able to approach the subject with much more deliberation and with a much better equipment than was available in France ; and their results are proportionally more convincing. Like Gibson and his co-workers, they produced in rabbits a condition closely resembling human influenza by means of filtered or unfiltered nasal secretions taken from human patients during the earliest stages of the attack. They provided independent confirmation of the discovery of Gibson and Bowman that "cultures" in Nogouchi medium were capable of transmitting the disease to animals, and showed that the anaerobic and filterable organism thus cultivated retained its activity after long exposure to glycerine and possessed antigenic properties. To the minute organism isolated by them in the course of this inquiry, they gave the name of Bacterium pneumosintes.

Their work received speedy confirmation at the hands of Dr. M. H. Gordon, C.M.G., F.R.S., in the course of an influenzal outbreak among the nursing staff of St. Bartholomew's hospital, London, in 1922. Still further support for a "filter-passer" as the virus of influenza was later provided by Sir Spenser Lister in South Africa. These independent inquiries, leading to similar findings in America, England and South Africa, go far to estab lish the "case" for a filterable virus as the causative agent of influenza ; but caution is still needed in drawing final conclusions until a more precise knowledge is available as to "filter-passers" in general (see FILTER-PASSING VIRUSES).

Epidemiology.

In the absence of final knowledge as to the causative agent, many points of fundamental importance still remain obscure.

The first wave coincided with the arrival of the first drafts of American troops in Europe, who must have brought into common circulation pathogenic strains long dormant in isolated and rela tively immunized communities. The crowded troopships afforded just the incubation places that would permit of the maturation of such an infection; and Europe, with its crowded concentration areas and billets, offered an unequalled opportunity for its spread. The last influenzal pandemic had occurred just 28 years bef ore. There might be a few scattered "carriers" and perhaps some residual immunity among the middle-aged and the elderly ; but the adolescents and the young adults would in 1918 be "virgin soil." It was just these lower age-groups that suffered most.

How, then, explain the second wave with its greater severity? —and the third? Surely, if immunity played a part, these waves should have been much less extensive, much more benign, and confined to those persons who had previously escaped. These are good, but not final, arguments. The passage of the first wave may have left behind it a virus of exalted virulence, many "carriers" and many "allergic" subjects whose behaviour to reinfection might betray the phenomena of hypersensitiveness of the respiratory surfaces and a tendency to inflammatory exudates on contact with the air-borne virus. Under such conditions a fresh outbreak would be specially likely to arise in the fall of the year, a period of rapid fluctuations of temperature when the chill evenings drive men into the warmth and close contact of crowded dug-outs, shelters and billets.

It is impossible to believe that the so-called "influenza" to which deaths were attributed every year between 1892 and 1918 was the same disease as the fulminating pandemic that followed. Apart from the extreme contrast in invasive power, the distri bution of "influenza" mortality by age-groups emphasizes the essential difference between, let us say, the death-rates for 1917 and 1918, the one having a preponderating death-rate amongst the old, the other, amongst the young. Such differences can hard ly leap into existence within a few months. The known facts of increase and diminution of bacterial virulence do not support the idea that such a vast alteration is probable or even possible in so short a time.

Acquired Immunity.

Evidence that morbidity and mortal ity were less marked, in the second wave, amongst those who had been attacked in the first, when thoroughly analysed (Rep. Min. Health, 1918-19), was found to indicate that "these data show a considerable immunizing power in the summer attacks and we conclude, although with natural hesitation, that it is probable, on the average, that an appreciable degree of active immunity was attained by those who passed through an attack in its first and mildest manifestations." The evidences for immunity are of varying efficiency in dif ferent places, and the populations of many areas show no tend ency to acquire resistance to infection as judged by a comparison between the behaviour of those attacked and those missed by the first wave when confronted by the second.

We believe these data to be unsound as a basis for comparison. It is highly probable that many persons were infected during the summer and yet failed to show appreciable illness. The vast difference that may exist between the numbers infected and the numbers affected by a bacterial invasion can be judged from what we know of the meningococcus and the diphtheria bacillus. And yet these latent infections may confer active immunity, as we know from the "Schick Reaction" in the case of diphtheria and from other examples. The mere fact of a previous "attack" is not a safe guide in classifying populations for inquiry as to their relative immunities. The best evidence of the acquisition of im munity is to be found in the phenomena of natural recovery of the individual and of the disappearance of pandemic waves f rom the community. The fact that these groups of pandemics are separated by long and fairly regular intervals, as a rule about 20 years, is not without significance in this connection, since at least this period might be necessary to reduce the residual "immune population" from the last pandemic to an ineffective number.

Artificial Immunity.

No vaccine can be entirely satisfac tory unless it is known to contain the virus or germ of the disease in question. The vaccine issued by the War Office and afterwards by the Ministry of Health was confessedly of a provisional nature since the causative agent was still uncertain. Its formula was as follows :— Unless Pfeiffer's bacillus be accepted as the causative agent, this vaccine must be described as consisting entirely of the "secon dary invaders." As such, its issue was entirely justifiable and its effects were such as might be expected: satisfactory in diminish ing complications and mortality but practically nil in preventing the disease. Vaccine, then, cannot, as a prophylactic, help us much at present ; nor can we, in the light of recent experience, hope for great results from general measures of hygiene.

Symptoms.

These vary somewhat in different epidemics but in the main they accord with the description given by Dr. Bruce Low from observations made in St. Thomas's hospital, London, in Jan. 1890 : The invasion is sudden ; the patients can generally tell the time when they developed the disease ; e.g., acute pains in the back and loins came on quite suddenly while they were at work or walking in the street, or in the case of a medical student, while playing cards, rendering him unable to continue the game. A workman wheeling a barrow had to put it down and leave it ; and an omnibus driver was unable to pull up his horses. This sudden onset is often accom panied by vertigo and nausea, and sometimes actual vomiting of bilious matter. There are pains in the limbs and general sense of aching all over ; frontal headache of special severity ; pains in the eyeballs, increased by the slightest movement of the eyes ; shiver ing ; general feeling of misery and weakness, and great depression of spirits, many patients, both men and women, giving way to weeping ; nervous restlessness ; inability to sleep, and occasionally delirium. In some cases catarrhal symptoms develop, such as running at the eyes, which are sometimes infected on the second day ; sneez ing and sore throat ; and epistaxis, swelling of the parotid and submaxillary glands, tonsilitis and spitting of bright blood from the pharynx may occur. There is a hard, dry cough of a paroxysmal kind, worst at night. There is often tenderness of the spleen, which is almost always found enlarged, and this persists after the acute symptoms have passed. The temperature is high at the onset of the disease. In the first twenty-four hours its range is from zoo° F. in mild cases to I05 ° F. in severe cases Several writers have distinguished four main varieties of the disease—namely, (I) nervous, (2) gastrointestinal, (3) respira tory, (4) febrile, a form chiefly found in children. Clifford Allbutt said, "Influenza simulates other diseases." Many forms are of typhoid or comatose types. Cardiac attacks are common, not from organic disease but from the direct poisoning of the heart muscle by influenza.

Perhaps the most marked feature of influenza, and certainly the one which victims have learned to dread most, is the prolonged debility and nervous depression that frequently follow an attack. In the Paris epidemic of 1890 the suicides increased 25%, a large proportion of the excess being attributed to nervous prostration caused by the disease. Of insanities traceable to influenza, melan cholia is twice as frequent as all other forms put together. Other common after-effects are neuralgia, dyspepsia, insomnia, weakness or loss of the special senses, particularly taste and smell, abdom inal pains, sore throat, rheumatism and muscular weakness. The feature most dangerous to life is the special liability of patients to inflammation of the lungs. This affection must be regarded as a complication rather than an integral part of the illness.

The deaths directly attributed to influenza vary in different epidemics and at different times in the same epidemic, but on the whole, are few in proportion to the number of cases. In the milder forms it offers hardly any danger to life if reasonable care be taken, but in the severer forms it is a fairly fatal disease. In eight London hospitals the case-mortality among in-patients in the 1890 outbreak was 34.5 per I,000; among all patients treated it was 1.6 per i,000. In the army it was rather less. ° The infectious character of influenza having been recognized, suggestions were made for its administrative control on the familiar lines of notification, isolation and disinfection, but this has not hitherto been found practicable.

There is no routine treatment for influenza except bed. In all cases bed is advisable, because of the danger of lung complica tions, and in mild ones it is sufficient. Severer ones must be treat ed according to the symptoms. Quinine has been much used. Modern "anti-pyretic" drugs have also been extensively employed, and when applied with discretion they may be useful, but patients are not advised to prescribe them for themselves.

BIBLIOGRAPHY.-In

addition to the ordinary text-books, see series Bibliography.-In addition to the ordinary text-books, see series of articles by experts on different aspects in The Practitioner (Lon don) for January 1907 ; F. G. Crookshank, Influenza, essays by sev eral authors (bibl.) (London, 1922) ; J. McIntosh, "Studies in the Etiology of Epidemic Influenza" (bibl.), Med. Res. Council Spec. Rep. Ser No. 63 (London, 1922) ; W. F. Vaughan, Influenza (bibl.) (Balti more, 1921) ; M. C. Winternitz, I. M. Wason and F. P. McNamara, The Pathology of Influenza (bibl.) (New Haven, 192o) ; Ministry of Health, Rep. on the Pandemic of Influenza, 1918-19 (London, 192o) Sir A. Newsholme and others, "Discussion on Influenza," Proc. Roy. Soc. Med. (London, 1918-19) . (S. L. C.) IN FORMA PAUPERIS: see PRACTICE AND PROCEDURE.

wave, disease, pandemic, amongst, virus, lungs and respiratory